Dabrafenib Mesylate

Bezeichnung:Dabrafenib Mesylate

CAS-Nr1195768-06-9

Englisch Name:Dabrafenib Mesylate

CBNumberCB72630077

SummenformelC24H24F3N5O5S3

Molgewicht615.66

MOL-Datei1195768-06-9.mol

Dabrafenib Mesylate physikalisch-chemischer Eigenschaften

Schmelzpunkt	>234oC (dec.)
storage temp.	Hygroscopic, -20°C Freezer, Under inert atmosphere
Löslichkeit	DMSO (Slightly, Heated), Methanol (Slightly)
Aggregatzustand	White solid.
Farbe	White to Off-White
Stabilität	Hygroscopic
InChIKey	YKGMKSIHIVVYKY-UHFFFAOYSA-N
SMILES	S(O)(=O)(=O)C.FC1C(=CC=CC=1C1N=C(C(C)(C)C)SC=1C1C=CN=C(N)N=1)NS(C1C(=CC=CC=1F)F)(=O)=O

Sicherheit

HS Code

2935909099

Gefahreninformationscode (GHS)

Dabrafenib Mesylate Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Dabrafenib mesylate, sold by GlaxoSmithKline under the trade name Tafinlar, was approved by the U.S. FDA in May 2013 for the treatment of metastatic BRAF-mutant melanoma. Dabrafenib reversibly inhibits the BRAF(V600E) mutant kinase as a selective ATP-competitive inhibitor which results in tumor regression.
Verwenden
Dabrafenib is an inhibitor of mutated BRAF kinase and has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma.
Definition
ChEBI: A methanesulfonate (mesylate) salt prepared from equimolar amounts of dabrafenib and methanesulfonic acid. Used for treatment of metastatic melanoma.
Synthese
Commercially available fluoroaniline 40 was first converted to sulfonamide 42 in 91% yield by treatment with 2,5-difluorobenzenesulfonyl chloride (41) in the presence of pyridine. Next, deprotonation of 2-chloro-4-methylpyrimidine (43) with lithium bis(trimethylsilyl)amide (LHMDS) followed by addition to ester 42 afforded chloropyrimidine 44 in 72% yield. Bromination followed by thiazole formation through the use of 2,2-dimethylpropanethioamide gave the penultimate target 45 in 80% over two steps. Chloropyrimidine 45 was subjected to SNAr conditions with ammonium hydroxide to furnish the aminopyrimidine in 88% yield, and this was followed by exposure to methanesulfonic acid to afford dabrafenib mesylate (VI) in 85% yield.
target
Raf
Lager
Store at -20°C
Einzelnachweise
[1]namba h, nakashima m, hayashi t, hayashida n, maeda s, rogounovitch ti, ohtsuru a, saenko va, kanematsu t, yamashita s. clinical implication of hot spot braf mutation, v599e, in papillary thyroid cancers. j. clin. endocrinol. metab. 2003; 88 (9): 4393–7.
[2]tan yh, liu y, eu kw, ang pw, li wq, salto-tellez m, iacopetta b, soong r. detection of braf v600e mutation by pyrosequencing. pathology 2008; 40 (3): 295–8.
[3]davies h, bignell gr, cox c, et al. mutations of the braf gene in human cancer. nature. 2002; 417: 949-954.
[4]ma xh, piao sf, dey s, mcafee q, karakousis g, villanueva j, hart ls, levi s, hu j, zhang g, lazova r, klump v, pawelek jm, xu x, xu w, schuchter lm, davies ma, herlyn m, winkler j, koumenis c, amaravadi rk. targeting er stress-induced autophagy overcomes braf inhibitor resistance in melanoma. j clin invest. 2014; 124(3): 1406-17.

Dabrafenib Mesylate Upstream-Materialien And Downstream Produkte

Dabrafenib Mesylate Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

1195768-06-9, Dabrafenib Mesylate Verwandte Suche:

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